Secretory granules released by cytotoxic T lymphocytes (CTLs) are powerful weapons against intracellular microbes and tumor cells. Despite significant progress, there is still limited information on the molecular mechanisms implicated in target-driven degranulation, effector cell survival and composition and structure of the lytic granules. Here, using a proteomic approach we identified a panel of putative cytotoxic granule proteins, including some already known granule constituents and novel proteins that contribute to regulate the CTL lytic machinery. Particularly, we identified galectin-1 (Gal1), an endogenous immune regulatory lectin, as an integral component of the secretory granule machinery and unveil the unexpected function of this lectin in regulating CTL killing activity. Mechanistic studies revealed the ability of Gal1 to control the non-secretory lytic pathway by influencing Fas-Fas ligand interactions. This study offers new insights on the composition of the cytotoxic granule machinery, highlighting the dynamic cross talk between secretory and non-secretory pathways in controlling CTL lytic function.
Documento: | Artículo |
Título: | Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery |
Autor: | Clemente, T.; Vieira, N.J.; Cerliani, J.P.; Adrain, C.; Luthi, A.; Dominguez, M.R.; Yon, M.; Barrence, F.C.; Riul, T.B.; Cummings, R.D.; Zorn, T.M.; Amigorena, S.; Dias-Baruffi, M.; Rodrigues, M.M.; Martin, S.J.; Rabinovich, G.A.; Amarante-Mendes, G.P. |
Filiación: | Instituto de Ciências Biomédicas, Universidade de São PauloSão Paulo, Brazil Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (INCT)São Paulo, Brazil Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Buenos Aires C1428, Argentina Instituto Gulbenkian de Ciência, Oeiras, Portugal Department of Genetics, Smurfit Institute, Trinity CollegeDublin, Ireland Centro de Terapia Celular e Molecular (CTCMol) and Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de MedicinaSão Paulo, Brazil Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São PauloSão Paulo, Brazil Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States Institut Curie, PSL Research University, INSERM U932, Paris Cedex, 05, France Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos AiresBuenos Aires C1428, Argentina |
Palabras clave: | Fas ligand; Fas protein, mouse; Fasl protein, mouse; galectin 1; tumor necrosis factor receptor superfamily member 6; animal; C57BL mouse; cell proliferation; chemistry; cytology; cytotoxic T lymphocyte; cytotoxicity; degranulation; gene expression profiling; gene expression regulation; genetics; immunology; knockout mouse; lymphocyte activation; male; metabolism; mouse; proteomics; secretory vesicle; signal transduction; Animals; Cell Degranulation; Cell Proliferation; Cytotoxicity, Immunologic; Fas Ligand Protein; fas Receptor; Galectin 1; Gene Expression Profiling; Gene Expression Regulation; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Proteomics; Secretory Vesicles; Signal Transduction; T-Lymphocytes, Cytotoxic |
Año: | 2017 |
Volumen: | 8 |
Número: | 12 |
Página de inicio: | e3176 |
DOI: | http://dx.doi.org/10.1038/cddis.2017.506 |
Título revista: | Cell death & disease |
Título revista abreviado: | Cell Death Dis |
ISSN: | 20414889 |
CAS: | galectin 1, 258495-34-0; Fas Ligand Protein; Fas protein, mouse; fas Receptor; Fasl protein, mouse; Galectin 1 |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v8_n12_pe3176_Clemente |